The humoral and cell-mediated immune responses decline with age in both animals and man. Many of the "diseases of ageing" are associated either directly or secondarily with the deterioration of the immune system. One of the causes for the reduced response is the inability of old lymphocytes to transform and proliferate after coming into contact with an antigen or mitogen. T-lymphocytes appear more severely affected by the aging process and old T-cells have markedly reduced responses to mitogens. The reduced mitogenic response is not due to the inability of old T-lymphocytes to bind mitogen but may be associated with the inability of the old cells to regulate their intracellular levels of cyclic-AMP and cyclic-GMP. These two cyclic-nucleotides are thought to be involed in the regulation of cell proliferation. A marked improvement in the in vitro proliferative response to mitogens is seen when 2-mercaptoethanol, an antioxidant, is added to cultures of old T-cells. In a preliminary in vivo study, some antioxidants, when added to the diets of mice, stimulated the humoral response of young mice and produced an elevated response throughout about 2/3 of the life of the animals. Older mice were not available for study. Experiments are proposed to determine if antioxidants added tn the diet 1) will improve the response of very young and very old mice, 2) will prevent the age-related decline from occurring, 3) will have an effect on memory cells and a secondary response. Experiments are also planned to determine which of the immunocompetent cells (A-cells, B-cells, T-cells) are influenced by antioxidants and by what mechanism the antioxidants stimulate immune responses. Two possible mechanisms, a direct effect on the cyclic-nucleotide system and the prevention of lipid peroxidation and hence membrane deterioration, will be investigated.